DESCRIPTION (adapted from the application): The rationale for establishing a new Core Laboratory devoted to One-carbon Metabolism is the enormous current interest in this area of research, not only by nutritional scientists, but also among the public at large. This is a result of two major developments in Nutritional Research over the past several years. The first is the recognition that about 75% of all births with neural tube defects may be prevented by periconceptional supplementation with folic acid. The second development is the identification of elevated plasma homocysteine levels as an independent risk factor for vascular disease. Since January 1997 there have been published over 1300 journal articles about folic acid and over 700 articles about homocysteine. At Vanderbilt we are fortunate to have a group of investigators who are among the leaders in studies of folate and one-carbon metabolism. The impetus to establish the one-carbon Core has been the desire to make this expertise available to other CNRU investigators. It is clear that patients with homocystinuria having very high levels of plasma homocysteine develop vascular occlusive disease at an early age if untreated. Recently, attention has been focused on patients with moderately elevated homocysteine levels (hyperhomocysteinemia) and an association with cardiovascular, cerebrovascular and peripheral vascular disease has been established. Even more recently, the increased levels of plasma homocysteine in patients with renal disease has suggested that this may be related to the high incidence of coronary heart disease in this group of patients. In addition, plasma homocysteine has been shown to be significantly elevated in patients with Alzheimer's disease and in dementia of Alzheimer's type.